This grant proposes studies of the characteristics and neuroendocrine control of sex differences in sensorimotor modulation of the startle reflex. Sensorimotor modulation is the process by which central inhibitory and facilitatory mechanisms adjust an organism's responsivity to sensory stimuli. This modulation is viewed as protective of some forms of information processing PPI is the normal inhibition of the startle reflex that occurs when the startling stimulus is preceded 30-500 msec by a weak prepulse. At shorter intervals (4-30 msec), very weak prepulses facilitate startle (PPF). The degree to which the weak prepulse inhibits or facilitates the motor response to the starting stimulus is an operational measure of sensorimotor modulation. The startle reflex and its modulation by prepulses have been studied for over 50 years. In an unexpected finding, robust sex differences in PPI and PPF were observed in normal subjects. Women exhibit significantly less PPI than do men, and exhibit PPF at prepulse intervals that are too long to elicit PPF in men. This finding has now been replicated 6 times, in 2 laboratories. No overall sex differences were found in a related measure of visuospatial priming. However, preliminary work suggests that sensorimotor modulation of both startle and visuospatial priming varies across the menstrual cycle, with less inhibition and more facilitation in luteal versus follicular phases. PPI in women was maximal in early follicular phase, and reached its nadir in midluteal phase. PPF was found only in mid-luteal phase. Menstrual patterns were noted in the change in PPI in a single test session: PPI declined across each session in early follicular phase, but this pattern reversed by luteal phase, when PPI increased across each session. Visuospatial priming also exhibited a menstrual pattern, with greater visuospatial facilitation in luteal versus follicular phase. Other recent work suggests that sex differences in PPI are lateralized, evident primarily in right (but not left) eyeblink, in which PPI is regulated largely by the left forebrain. All preliminary work was designed to assess PPI, and thus the stimuli used did not allow a full assessment of PPF. Furthermore, limited resources for these unfunded studies precluded hormonal assays to verify menstrual cycle phase or ovulation. The present studies will fully assess sex and menstrual patterns of inhibition and facilitation of startle and visuospatial priming, using optimal paradigmatic designs and hormonal assays, and bilateral startle measures. PPI, PPF and visuospatial priming will be measured in men, and in women across the menstrual cycle, with documentation of luteal hormone (LH) surge. Neuropsychological measures with reported sex- and menstrual patterns will be assessed, in addition to specific psychometric measures, and results will be correlated with changes in PPI, PPF and visuospatial priming. Sex differences, menstrual cyclicity and laterality of sensorimotor modulation offer a unique opportunity to examine sexual dimorphism in fundamental neurobiological processes that are critical determinants of information processing, and which may be directly relevant to sex differences in the presentation and treatment of psychiatric disorders.